The Promise of Therapeutic Psilocybin: An Evaluation of the 134 Clinical Trials, 54 Potential Indications, and 0 Marketing Approvals on ClinicalTrials.gov

Abstract

Introduction

Psilocybin, a tryptamine psychedelic, has been touted in the media both historically and recently as a potential game-changing mental health therapeutic. ClinicalTrials.gov has over one hundred and thirty psilocybin clinical trials listed covering the last twenty years. The single most important aspect of any therapeutic is to gain approval for marketing and thus enter the real-world phase of development. A typical new chemical entity progresses from inception to US Food and Drug Administration (FDA) approval in approximately 12 years and seeks approval for a single indication.

Methods

An observational study was conducted with the available information on the ClinicalTrials.gov site to observe the extent of progress made demonstrating the clinical utility of psilocybin.

Results

The results showed 134 psilocybin trials typically unblinded studies of 10–20 participants, recruited over years at a single site. Additionally, there have been only three advanced trials (1 Phase 2/3 and 2 Phase 3) submitted, and only in the last two years.

Discussion

The hundreds of psilocybin clinical trials initiated over the past twenty years comprising a myriad of potential indications may actually be slowing this potential game-changing mental health therapeutic agent’s approval and is costing excessive amounts of capital. To fully evaluate the actual potential of psilocybin, purposeful clinical trials need to be designed well, executed efficiently, and analyzed utilizing sequential and statistically valid processes for each potential indication. This will require a change from the current exploratory forays to defined, well-funded, sequential pharmaceutical development practices, including adequate and appropriate blinding of studies, statistical design to determine the number of participants and more importantly, professional expertise in conducting multicenter trials. Unfortunately, these results demonstrate little real progress towards FDA approval of psilocybin and a field with no clear direction forward.

Keywords:

• psilocin
• psychedelic
• FDA approval
• mental health

Abbreviations

CAGR, compound annual growth rate; CI, confidence interval; CMS, Centers for Medicare & Medicaid Services; DEA, US Drug Enforcement Agency; FDA, US Food and Drug Administration; FDAAA 801, Food and Drug Administration Amendments Act; GCP, Good Clinical Practice; IRB, institutional review board; MDD, major depressive disorder; N/A, not applicable; NCE, new chemical entity; NDA, new drug application; PRO, patient-reported outcomes; TRD, treatment-resistant depression; US, United States of America.

Data Sharing Statement

The dataset generated and analyzed during the current study is available from the corresponding author on reasonable request.

Ethics Approval

As this study utilized public, non-human subject data not constituting human participant research, does not require IRB or ethics committee approval, it was therefore not submitted for review, nor did it receive an approval by any IRB.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All authors are currently employed by and are stockholders in PsyBio Therapeutics, Inc. The authors report no other conflicts of interest in this work.

Additional information

Funding

This paper was funded by PsyBio Therapeutics, Inc.